Dry eye disease (DED) is a complex, multifactorial pathology characterized by corneal epithelium lesions and inflammation. The aim of the present study was to evaluate the efficacy of a cationic emulsion of cyclosporine A (CsA) in a mouse model that mimics severe dry eye. Eight to 12-week-old female C57BL/6N mice with tail patches of scopolamine were housed in controlled environment chambers to induce dry eye. At day three, following dry eye confirmation by corneal fluorescein staining (CFS, score 0-15) and phenol red thread (PRT) lacrimation test, the mice (n = 10/gp) were either treated 3 times a day in both eyes with drug-free cationic emulsion, a 0.1% CsA cationic emulsion, or 1% methylprednisolone (positive control), or non-treated. Aqueous tear production and CFS scores were evaluated at baseline and throughout the treatment period. The lacrimation test confirmed the scopolamine-induced decrease in aqueous production by the lacrimal gland. A reduction of 59% in induced-CFS was observed following topical treatment with 0.1% CsA. The beneficial effect of the cationic emulsion vehicle itself on keratitis was also clearly evidenced by its better performance over 1% methylprednisolone, -36%, vs. -28% on the CFS scores, respectively. This study indicates that the cationic emulsion of CsA (0.1%) was a very effective formulation for the management of corneal epithelium lesions in a severe DED mouse model. In addition, it performed better than a potent glucocorticosteroid (1% methylprednisolone). This cationic emulsion of CsA (0.1%), combining CsA and a tear film oriented therapy (TFOT), i.e. with vehicle properties that mechanically stabilize the tear film, represents a promising new treatment strategy for the management of the signs of dry eye.

This study indicated that use of BAK has negative effects on the ocular surface under normal and dry eye conditions, even if the association with bimatoprost does not confirm the same results. A BAK-free travoprost preparation showed positive effects on tear secretion and corneal protection.

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PurposeDry eye syndrome is a common disease with multifactorial causes. Symptoms typically include irritation, dryness, burning and decreased or fluctuating vision. Anti‐inflammatory drugs are widely used for the treatment of the inflammation produced by the disease with corticoid or cyclosporine A (CsA). Restasis® (Allergan), a CsA emulsion, was approved by the FDA but is not available in Europe. Here we propose to show the action of Optimmune® (MSD Animal Health) a marketed veterinary ophthalmic ointment that contains CsA in an experimental mouse model of dry eye induced by scopolamine, a tropane alkaloid drug with muscarinic antagonist effects.MethodsAnimals were divided in three groups of ten pigmented mice: Two groups were exposed to desiccating conditions (relative humidity <25%, air‐flow 15 L/min, temperature 20‐22°C) with transdermal scopolamine administration (0.5 mg/72 h) for 14 days. Animals were treated topically three times a day with 0.2% CsA ointment or vehicle. Controls were saline‐treated animals placed in a normal environment. Tear production was measured with the phenol red thread test, corneal defects were examined by slit‐lamp observation using blue light after 0.5% fluorescein eye drop. These examinations were performed in both eyes before exposure and on days 3, 7 and 14. A histological study was performed at the end of the study.ResultsCyclosporine A eye ointment appeared to show efficacy in this model.ConclusionsCyclosporine A eye ointment significantly reduced clinical signs of dry eye by decreasing corneal defect more than cyclosporine A ophthalmic emulsion (internal studies).

Purpose Dry eye syndrome is a relatively common disease with multifactorial causes. It has been shown that rodent models of dry eye experimentally induced by scopolamine, a tropane alkaloid drug with muscarinic antagonist effects, could be helpful to test and select therapeutic candidates in the disease. Here we propose to show the action of cyclosporine A, an inhibitor of T‐cell activation and inflammatory cytokine production, after oral and topical administrations. Methods Experimental dry eye was induced in female albino rats by a systemic and continuous delivery of scopolamine (20 mg/day) over 21 days via osmotic pumps implanted subcutaneously on day 1. Animals were divided in three groups of five animals: The first two groups were instilled either saline or cyclosporine 0.05% eye drops and the third group received 20mg/kg/day cyclosporine by oral administration. Tear production was measured with the phenol red thread test, tear break‐up time was studied under slit‐lamp, and corneal defects were examined by slit‐lamp observation using blue light after 0.5% fluorescein eye drop instillation and in vivo confocal microscopy. These examinations were performed in both eyes at baseline and on days 7, 14 and 21. Results Cyclosporine orally or topically administered significantly reduced clinical signs of dry eye by increasing lacrimation and decreasing corneal defect. Conclusion Cyclosporine appears to show efficacy in this model, regardless of the mode of administration. Commercial interest